A Study to Evaluate Safety, Tolerability, and Preliminary... | NCT05435339

NCT05435339

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description
2021-006692-42	EudraCT Number
1005700	Other Identifier	IRAS ID; UK Research Summaries Database
2022-502419-12-00	EU Trial (CTIS) Number

Status Module

Name	Class
BioNTech SE	INDUSTRY

Description Module

Label	Type	Description	Intervention Names
GEN1053 Monotherapy	Experimental		Biological: GEN1053

Name	Type	Description	Arm Group Labels	Other Names
GEN1053	Biological	GEN1053 will be administered as an intravenous (IV) infusion every 3rd week. The dose levels will be determined by the starting dose and the escalation steps taken in the trial.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Dose Limiting Toxicities (DLTs)	The occurrence of any of the following toxicities, assessed as related to trial treatment, were considered DLTs: All Grade 5 events, Grade 4 anaphylaxis, infusion-related reactions and neutropenia for ≥7 days, Grade 3/4 febrile neutropenia, Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with clinically significant bleeding, Grade 4 anemia, Grade 4 aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin elevation/Grade 3 that did not recover to ≤Grade 1 within 14 days, AST or ALT elevations ≥Grade 2 with concomitant bilirubin >2.0×upper limit of normal with no signs of cholestasis, any Grade 4 immune-related adverse event (irAE), Grade 3 irAEs that did not improve to ≤Grade 1 within 7 days (with exceptions), Grade 4 cytokine release syndrome (CRS), Grade 3 CRS not resolved to ≤Grade 2 within 48 hrs following adequate intervention, any other ≥Grade 3 nonhematological adverse event (AE) during the first GEN1053 treatment cycle (with exceptions), cycle=3 weeks.	Day 1 up to Day 21
Number of Participants With At Least One Treatment-emergent Adverse Event (TEAE)	An adverse event (AE) was any untoward medical occurrence in a participant or clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE was therefore any unfavorable and unintended sign (including an abnormal safety laboratory parameter finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A TEAE was defined as an AE occurring or worsening after first dose. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.	Up to approximately 1.5 years

Secondary Outcomes

Measure	Description	Time Frame
Clearance (CL) of GEN1053	Venous blood samples were collected for analyzing the pharmacokinetics (PK) of GEN1053.	Cycle 1 and Cycle 3 (cycles were 3 weeks)
Volume of Distribution (Vz) of GEN1053

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria:

For both the Dose Escalation and Expansion parts:

Be ≥18 years of age.
Have measurable disease according to RECIST 1.1
Provide all pre-baseline scans since failure of last prior therapy (ie radiographic PD), if available
Have Eastern Cooperative Oncology Group performance status ≤1.
Have organ and bone marrow function as follows:

Bone marrow / hematological function:

Absolute neutrophil count (ANC) ≥1.5×10^9/L
Hemoglobin ≥9.0 g/dL
Platelet count ≥150×10^9/L

Liver function:

Total bilirubin ≤ upper limit of normal (ULN)
Alanine aminotransferase ≤1.5×ULN
Aspartate aminotransferase ≤1.5×ULN
Albumin ≥30 g/L

Coagulation status:

Prothrombin time (PT)/International normalized ratio ≤1.5
Activated partial thromboplastin time (aPTT) ≤1.5×ULN
Renal function: Glomerular filtration rate ≥45 mL/min/1.73 m², according to the abbreviated Modification of Diet in Renal Disease equation

For Monotherapy Dose Escalation (phase 1) only:

Subjects with histologically or cytologically confirmed non-CNS solid tumors that are metastatic or advanced.
Subjects who have progressed on standard of care therapy or for whom there is no available standard therapy likely to provide clinical benefit, or who are not candidates for or refuse such available therapy, and for whom, in the opinion of the investigator, experimental therapy with GEN1053 may be beneficial.
Fresh biopsies mandatory for all patients in Monotherapy Dose Escalation

For the Expansion part Only:

•Subjects with histologically or cytologically confirmed diagnosis of recurrent, unresectable or metastatic HNSCC, who have progressed on standard of care therapy or do not have any further available standard therapy or are not candidates for or refuse standard therapy (if subjects had access), and for whom experimental therapy with GEN1053 may be beneficial in the opinion of the investigator.

Key Exclusion Criteria (all parts):

Has uncontrolled intercurrent illness, including but not limited to:
- Ongoing or active infection requiring IV treatment with anti-infective therapy administered less than 2 weeks prior to first dose.
- Symptomatic congestive heart failure (Grade III or IV as classified by the New York Heart Association), unstable angina pectoris or cardiac arrhythmia.
- Uncontrolled hypertension defined as systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥100 mm Hg, despite optimal medical management.
- Prolonged QTc interval at baseline of ≥470 milliseconds using Fridericia's QT correction formula.
- Ongoing or recent (within 1 year) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for irAEs.
- History of grade 3 or higher irAEs that led to treatment discontinuation of a CPI.
- History of chronic liver disease or evidence of hepatic cirrhosis.
- Evidence of interstitial lung disease.
- Ongoing pneumonitis or history of non-infectious pneumonitis that has required steroids.
- Known platelet function defects
Prior therapy:
- Radiotherapy within 14 days prior to first GEN1053 administration. Palliative radiotherapy will be allowed.
- Treatment with an anti-cancer agent (within 28 days or after at least 5 half-lives of the drug, whichever is shorter), prior to GEN1053 administration.
- Subject with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first treatment. Inhaled or topical steroids, and adrenal or pituitary replacement steroid > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Facility	Status	City	State	ZIP	Country	Contacts
Yale University		New Haven	Connecticut	06510	United States
Sarah Cannon Research Institute

Label	URL
Results Summary in Plain Language	View source

Arm/Group Information

ID	Title	Description
FG000	GEN1053 Dose Level 1 Once Every 3 Weeks (Q3W)	Participants with malignant solid tumors were treated with dose level 1 of GEN1053 Q3W by intravenous (IV) infusion. Dose Level 1 was the lowest dose, and doses were increased incrementally up to Dose Level 8, which was the highest dose.
FG001	GEN1053 Dose Level 2 Q3W	Participants with malignant solid tumors were treated with dose level 2 of GEN1053 Q3W by IV infusion. Dose Level 1 was the lowest dose, and doses were increased incrementally up to Dose Level 8, which was the highest dose.
FG002	GEN1053 Dose Level 3 Q3W	Participants with malignant solid tumors were treated with dose level 3 of GEN1053 Q3W by IV infusion. Dose Level 1 was the lowest dose, and doses were increased incrementally up to Dose Level 8, which was the highest dose.
FG003	GEN1053 Dose Level 4 Q3W	Participants with malignant solid tumors were treated with dose level 4 of GEN1053 Q3W by IV infusion. Dose Level 1 was the lowest dose, and doses were increased incrementally up to Dose Level 8, which was the highest dose.
FG004	GEN1053 Dose Level 5 Q3W	Participants with malignant solid tumors were treated with dose level 5 of GEN1053 Q3W by IV infusion. Dose Level 1 was the lowest dose, and doses were increased incrementally up to Dose Level 8, which was the highest dose.
FG005	GEN1053 Dose Level 6 Q3W	Participants with malignant solid tumors were treated with dose level 6 of GEN1053 Q3W by IV infusion. Dose Level 1 was the lowest dose, and doses were increased incrementally up to Dose Level 8, which was the highest dose.
FG006	GEN1053 Dose Level 7 Q3W	Participants with malignant solid tumors were treated with dose level 7 of GEN1053 Q3W by IV infusion. Dose Level 1 was the lowest dose, and doses were increased incrementally up to Dose Level 8, which was the highest dose.
FG007	GEN1053 Dose Level 8 Q3W	Participants with malignant solid tumors were treated with dose level 8 of GEN1053 Q3W by IV infusion. Dose Level 1 was the lowest dose, and doses were increased incrementally up to Dose Level 8, which was the highest dose.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	GEN1053 Dose Level 1 Q3W	Participants with malignant solid tumors were treated with dose level 1 of GEN1053 Q3W by IV infusion. Dose Level 1 was the lowest dose, and doses were increased incrementally up to Dose Level 8, which was the highest dose.
BG001	GEN1053 Dose Level 2 Q3W

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type	Title	Description	Population Description	Reporting Status	Anticipated Posting Date	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Time Frame	Units Analyzed	Denominator Units Selected	Arm/Group Information	Denominators	Classes	Analyses
Primary	Number of Participants With Dose Limiting Toxicities (DLTs)	The occurrence of any of the following toxicities, assessed as related to trial treatment, were considered DLTs: All Grade 5 events, Grade 4 anaphylaxis, infusion-related reactions and neutropenia for ≥7 days, Grade 3/4 febrile neutropenia, Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with clinically significant bleeding, Grade 4 anemia, Grade 4 aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin elevation/Grade 3 that did not recover to ≤Grade 1 within 14 days, AST or ALT elevations ≥Grade 2 with concomitant bilirubin >2.0×upper limit of normal with no signs of cholestasis, any Grade 4 immune-related adverse event (irAE), Grade 3 irAEs that did not improve to ≤Grade 1 within 7 days (with exceptions), Grade 4 cytokine release syndrome (CRS), Grade 3 CRS not resolved to ≤Grade 2 within 48 hrs following adequate intervention, any other ≥Grade 3 nonhematological adverse event (AE) during the first GEN1053 treatment cycle (with exceptions), cycle=3 weeks.	Measured in the Safety Analysis Set, which included all participants who received at least 1 dose of trial drug. Participants were analyzed according to the actual trial treatment received.	Posted		Count of Participants		Participants		Day 1 up to Day 21

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	GEN1053 Dose Level 1 Q3W	Participants with malignant solid tumors were treated with dose level 1 of GEN1053 Q3W by IV infusion. Dose Level 1 was the lowest dose, and doses were increased incrementally up to Dose Level 8, which was the highest dose.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Large intestine perforation	Gastrointestinal disorders	27.0	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Groin pain	Musculoskeletal and connective tissue disorders	27.0	Systematic Assessment

Title	Organization	Phone	Extension	Email
CLINICAL TRIAL INFORMATION	Genmab	+45 7020 2728		clinicaltrials@genmab.com

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	May 7, 2024	Jan 23, 2025	Prot_SAP_000.pdf

ID	Title	Description
OG000	GEN1053 Dose Level 1 Q3W	Participants with malignant solid tumors were treated with dose level 1 of GEN1053 Q3W by IV infusion. Dose Level 1 was the lowest dose, and doses were increased incrementally up to Dose Level 8, which was the highest dose.
OG001	GEN1053 Dose Level 2 Q3W	Participants with malignant solid tumors were treated with dose level 2 of GEN1053 Q3W by IV infusion. Dose Level 1 was the lowest dose, and doses were increased incrementally up to Dose Level 8, which was the highest dose.
OG002	GEN1053 Dose Level 3 Q3W	Participants with malignant solid tumors were treated with dose level 3 of GEN1053 Q3W by IV infusion. Dose Level 1 was the lowest dose, and doses were increased incrementally up to Dose Level 8, which was the highest dose.
OG003	GEN1053 Dose Level 4 Q3W	Participants with malignant solid tumors were treated with dose level 4 of GEN1053 Q3W by IV infusion. Dose Level 1 was the lowest dose, and doses were increased incrementally up to Dose Level 8, which was the highest dose.
OG004	GEN1053 Dose Level 5 Q3W	Participants with malignant solid tumors were treated with dose level 5 of GEN1053 Q3W by IV infusion. Dose Level 1 was the lowest dose, and doses were increased incrementally up to Dose Level 8, which was the highest dose.
OG005	GEN1053 Dose Level 6 Q3W	Participants with malignant solid tumors were treated with dose level 6 of GEN1053 Q3W by IV infusion. Dose Level 1 was the lowest dose, and doses were increased incrementally up to Dose Level 8, which was the highest dose.
OG006	GEN1053 Dose Level 7 Q3W	Participants with malignant solid tumors were treated with dose level 7 of GEN1053 Q3W by IV infusion. Dose Level 1 was the lowest dose, and doses were increased incrementally up to Dose Level 8, which was the highest dose.
OG007	GEN1053 Dose Level 8 Q3W	Participants with malignant solid tumors were treated with dose level 8 of GEN1053 Q3W by IV infusion. Dose Level 1 was the lowest dose, and doses were increased incrementally up to Dose Level 8, which was the highest dose.